Physical exercise is considered to be beneficial for cardiovascular health. Nevertheless, the underlying specific molecular mechanisms still remain unexplored. In this study, we aimed to investigate the effects of voluntary exercise on vascular mechanical properties and gene regulation patterns in spontaneously hypertensive rats. By using ultrasound biomicroscopy in an ex vivo perfusion chamber, we studied the distensibility of the thoracic aorta. Furthermore, exercise-induced gene regulation was studied in aortae, using microarray analysis and validated with real-time PCR. We found that distensibility was significantly improved in aortas from exercising compared with control rats (P < 0.0001). Exercising rats demonstrated a striking pattern of coordinated downregulation of genes belonging to the heat shock protein family. In conclusion, voluntary exercise leads to improved vessel wall distensibility and reduced gene expression of heat shock protein 60 and 70, which may indicate decreased oxidative stress in the aortic vascular wall.

In the present study, we have developed and demonstrated a coronary artery imaging protocol in rats using transthoracic high-frequency CDE (colour Doppler echocardiography) to investigate the potential direct effects of exercise on CFVR (coronary flow velocity reserve). SHR (spontaneously hypertensive rats) performed voluntary exercise for 6 weeks. Rats were then submitted to ultrasonographic examination and CFVR measurements. The LAD (left anterior descending coronary artery) was visualized using transthoracic CDE in a modified parasternal long-axis view. Doppler measurement was made in mid-LAD during baseline and adenosine-induced hyperaemic condition. Gene and protein expression in cardiac tissue were studied using real-time PCR and immunohistochemistry. Adenosine infusion significantly (P<0.001, as determined by ANOVA) decreased HR, without affecting blood pressure in anaesthetized SHR. A significantly greater adenosine dose-dependent response was seen in exercised rats compared with controls (P=0.02, as determined by ANOVA). The baseline flow velocity in mid-LAD was 0.33+/-0.06 and 0.41+/-0.14 m/s in the exercised and control animals respectively (P value was not significant). The maximum adenosine-induced response was reached at a dose of 140 microg.kg-1 of body weight.min-1, and CFVR averaged at 2.6+/-0.53 and 1.5+/-0.24 in exercised and control animals respectively (P<0.01). Gene expression of CuZnSOD was up-regulated by 21% in exercised animals compared with controls (1.1+/-0.16 compared with 0.89+/-0.09; P<0.01), whereas eNOS expression was unchanged. In conclusion, CFVR in rats can be non-invasively assessed using CDE with high feasibility. Physical exercise is associated with improved CFVR and antioxidative capacity in SHR.

Forced training has been shown to have beneficial vascular effects in various animal exercise models. In the present study, we explored possible physiological and molecular effects of voluntary physical exercise on various vascular beds. SHR (spontaneously hypertensive rats) performed voluntary exercise for 5 weeks in a computerized wheel cage facility. Ex vivo myograph studies revealed an increased sensitivity of the ACh (acetylcholine)-mediated vasodilation in resistance arteries of the exercised animals (ED50=15.0+/-3.5 nmol/l) compared with the controls (ED50=37.0+/-8.8 nmol/l; P=0.05). The exercise/control difference was abolished after scavenging reactive oxygen radicals. In conduit arteries, ACh induced a similar vasodilatory response in both groups. The in vivo aortic wall stiffness, assessed by means of Doppler tissue echography, was significantly lower in the exercising animals than in controls. This was demonstrated by significantly increased peak systolic aortic wall velocity (P=0.03) and the velocity time integral (P=0.01) in exercising animals compared with controls. The relative gene expression of eNOS (endothelial nitric oxide synthase) was similar in both groups of animals, whereas Cu/ZnSOD (copper/zinc superoxide dismutase) gene expression was significantly increased (+111%; P=0.0007) in the exercising animal compared with controls. In conclusion, voluntary physical exercise differentially improves vascular function in various vascular beds. Increased vascular compliance and antioxidative capacity may contribute to the atheroprotective effects associated with physical exercise in conduit vessels.